ArticleAutophagy2018
TGFB1 is secreted through an unconventional pathway dependent on the autophagic machinery and cytoskeletal regulators.
Article in Autophagy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
What it found
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Who cites it
78 citing papers in PubMed, 126 citations in OpenAlex.
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- Pathological Interplay of ROS With Myofibroblasts: An Impediment to Corneal Restitution.Oxidative medicine and cellular longevity · 2026Review
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- New therapeutic approaches for fibrosis: harnessing translational regulation.Trends in molecular medicine · 2025Review
- Fibrosis: cross-organ biology and pathways to development of innovative drugs.Nature reviews. Drug discovery · 2025Review
- The Role of Autophagy in the Mineralization Process of Bone and Dentin.International journal of molecular sciences · 2025Review
- Metabolic reaction fluxes as amplifiers and buffers of risk alleles for coronary artery disease.Molecular systems biology · 2025Article
- Unconventional secretion of PARK7 requires lysosomal delivery via chaperone-mediated autophagy and specialized SNARE complex.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Review
- Single-cell transcriptomic profiling of heart reveals ANGPTL4 linking fibroblasts and angiogenesis in heart failure with preserved ejection fraction.Journal of advanced research · 2025Article
- Presenilins as hub proteins controlling the endocytic and autophagic pathways and small extracellular vesicle secretion.Journal of extracellular vesicles · 2025Article
- Mechanisms of prostatic inflammation-mediated male lower urinary tract symptoms.American journal of clinical and experimental urology · 2025Review
- Extracellular vesicles: cargo loading, degradation and secretory pathways, and their intersection with autophagy.Extracellular vesicles and circulating nucleic acids · 2025Review
18 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TGFB1 (transforming growth factor beta 1) is a potent cytokine playing a driving role in development, fibrosis and cancer. It is synthesized as prodomain-growth factor complex that requires tethering to LTBP (latent transforming growth factor beta binding protein) for efficient secretion into the extracellular space. Upon release, this large latent complex is sequestered by anchorage to extracellular matrix (ECM) networks, from which the mature growth factor needs to be activated in order to reach its receptors and initiate signaling. Here, we uncovered a novel intracellular secretion pathway by which the latent TGFB1 complex reaches the plasma membrane and is released from fibroblasts, the key effector cells during tissue repair, fibrosis and in the tumor stroma. We show that secretion of latent TGFB1, but not of other selected cytokines or of bulk cargo, is regulated by fibroblast-ECM communication through ILK (integrin linked kinase) that restricts RHOA activity by interacting with ARHGAP26/GRAF1. Latent TGFB1 interacts with GORASP2/GRASP55 and is detected inside MAP1LC3-positive autophagosomal intermediates that are secreted by a RAB8A-dependent pathway. Interestingly, TGFB1 secretion is fully abrogated in human and murine fibroblasts and macrophages that lack key components of the autophagic machinery. Our data demonstrate an unconventional secretion mode of TGFB1 adding another level of control of its bioavailability and activity in order to effectively orchestrate cellular programs prone to dysregulation as seen in fibrosis and cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.